Male sexual dysfunction, in particular erectile dysfunction, is attributed to various causes such as aging, operation of prostate gland, injury of nerve cord, and diabetes. However, what is common in these causes is that a decrease of blood flow into the corpus cavernosum penis is the direct cause. As one of methods of treating it, administration of a vasodilator such as prostaglandin E1 (hereinafter abbreviated as PGE1) has been considered effective (DICP—The animal of Pharmacotherapy, 5, 363 (1991)). However, PGE1 has problems that it is attended with pain (angialgia) upon administration, that the drug itself is unstable and so forth.
On the other hand, it has been found that prostaglandin E2 (hereinafter, abbreviated as PGE2) that has oxytocic effect also has utillity for erectile dysfunction. This has made it unclear whether or not the erectile dysfunction improving action of PGE1 is simply based on its vasodilating action (WO93/00894).
PGE2 is known to be as a metabolite in the cascade of arachidonic acid and have various activities such as cytoprotection, oxytocic effect, algesic effect, promotion of vermicular movement of digestive tract, arousal effect, supression of gastric-acid secretion, hypotensive activity, and diuretic action.
Studies in recent years have revealed that PGE2 receptores have subtypes that play different roles from each other. Currently known subtypes are roughly classified into four groups called EP1, EP2, EP3, and EP4, respectively (Negishi M. et al, J. Lipid Mediators Cell Signaling 12, 379-391 (1995)). Examination of separate roles of these receptors with compounds that bind to specific receptors and finding compounds not to bind any other subtype receptors has made it possible to obtain drugs having less side effects.
Recently, an application disclosing that the compounds having an ω-chain of PGE2 modified with a hydroxyl group have an effect on erectile dysfunction equivalent to that of PGE1 and are less irritating has been laid open to public inspection. It also describes that the compounds disclosed therein are EP2-specific (cf., WO99/02164).
Furthermore, the compounds used in the present invention represented by the formula (I) are the compounds described in Example 17 and 17(1) in the specification of Europian Patent Publication No. 860430.